This application for re-selection as a Diabetes TrialNet Clinical Center consist of (1) a proposed clinical trial (2) a description of our activities in the conduct of Type 1 diabetes clinical research (3) a description of our recruitment efforts, and (4) a description of the clinical facilities available for the conduct of TrialNet protocols. Previous studies have demonstrated that short term administration of anti-T cell, anti-B cell, and antigen-based therapy at least temporarily alters the course of beta cell destruction. Extending therapeutic benefits will likely require combination therapy such as elimination of the T effector response, protection of beta cells, activation of T regulatory cells, and enhancement of insulin action. TrialNet and other groups have successfully developed a platform to rapidly test therapies in newly diagnosed subjects. We believe that systematic testing of a wide variety of agents and careful use of clinical samples for exploratory analysis of data is the only way forward. To that end, we propose to test the effect of Tocilizumab (Anti-IL6Rab) on recently diagnosed subjects with Type 1 diabetes to determine whether it will preserve beta cell function. Our selection of Anti- IL6Rab is based on the following observations: (1) mechanistically, Anti-IL6Rab may have several important effects both as a therapy promoting the activity of T-regulatory cells allowing prolonged remission of disease, and as an anti-inflammatory altering the local pancreatic inflammatory infiltrate allowing enhanced beta cell function and/or allowing enhanced insulin action, (2) there is clinical safety data on the use of Anti-IL6Rab including data in children, (3) Anti-IL6Rab is clinically efficacious in treatment of other autoimmune diseases. The specific aims of this trial are to: ( Demonstrate the short term safety of Anti-IL6Rab in newly diagnosed patients, ( Demonstrate the efficacy of Anti-IL6Rab in newly diagnosed patients with respect to preservation of beta cell function ( Test the impact of Anti-IL6Rab therapy and response to therapy on measures associated with our primary hypothesized mechanism of action - promoting the activity of T regulatory cells. PUBLIC HEALTH RELEVANCE: Type 1 diabetes involves immune mediated destruction of insulin producing beta cells leading to lifelong dependence upon exogenous insulin. T1DM is a particular burden to children and their families, representing one of the most common chronic childhood diseases. A therapy that could delay or halt beta cell destruction would significantly improve the day-to-day management for subjects with diabetes and reduce long-term complications, thereby having significant clinical impact on patients with T1DM.